Recombinant Human IL-8/CXCL8

Interleukin-8 (IL-8), also known as CXCL8, GCP-1, and NAP-1, is a widely expressed proinflammatory member of the CXC family of chemokines. Near its N-terminus, this 8-9 kDa chemokine contains an ELR motif which is important for its angiogenic properties ^[1]. IL-8/CXCL8 can associate into a homodimer or a heterodimer with CXCL4/PF4 ^[2], and it can also interact with matrix and cell surface glycosaminoglycans ^[3]. Mature human IL-8/CXCL8 shares 65%-69% amino acid (aa) sequence identity with canine, feline, and porcine IL-8/CXCL8 ^[4]. There is no IL-8/CXCL8 gene counterpart in rodent. N-terminal truncation by multiple proteases generates a range of shorter forms, and an alternative splice form of human IL-8/CXCL8 carries an eleven aa substitution at the C-terminus ^[5]. The bioactivity of IL-8/CXCL8 is regulated by these truncations, by IL-8/CXCL8 citrullination at Arg5 (N-terminal to the ELR motif) ^[6], and by the decoy receptor DARC ^[7]. IL-8/CXCL8 effects are mediated through CXCR1/IL-8 RA, which is also used by CXCL6, and through CXCR2/IL-8 RB, which is used by multiple CXC chemokines ^[1]. CXCR1 and CXCR2 associate into functional homodimers and heterodimers with each other ^[8]. Through both CXCR1 and CXC R2, CXCL8 promotes neutrophil adhesion to the vascular endothelium and migration to sites of inflammation ^[9]. It triggers the antimicrobial activation of neutrophils through CXCR1 ^[10].

Reference

[1]. Lazennec, G. and A. Richmond (2010) Trends Mol. Med. 16:133.

[2]. Nesmelova, I.V. et al. (2005) J. Biol. Chem. 280:4948.

[3]. Pichert, A. et al. (2012) Biomatter 2:142.

[4]. Schmid, J. and C. Weissmann (1987) J. Immunol. 139:250.

[5]. Mortier, A. et al. (2008) Pharmacol. Ther. 120:197.

[6]. Proost, P. et al. (2008) J. Exp. Med. 205:2085.

[7]. Neote, K. et al. (1994) Blood 84:44.

[8]. Munoz, L.M. et al. (2009) J. Immunol. 183:7337.

[9]. Gerszten, R.E. et al. (1999) Nature 398:718.

[10]. Jones, S.A. et al. (1996) Proc. Natl. Acad. Sci. USA 93:6682.